Article

Methane and Hydrogen Positivity on Breath Test Is Associated With Greater Body Mass Index and Body Fat

March 2013
The Journal of Clinical Endocrinology and Metabolism 98(4)

DOI:10.1210/jc.2012-3144

Source
PubMed

Authors:

Ruchi Mathur

Cedars-Sinai Medical Center

James Mirocha

Cedars-Sinai Medical Center

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Context: Colonization of the gastrointestinal tract with methanogenic archaea (methanogens) significantly affects host metabolism and weight gain in animal models, and breath methane is associated with a greater body mass index (BMI) among obese human subjects. Objective: The objective of the study was to characterize the relationship between methane and hydrogen on breath test (as a surrogate for colonization with the hydrogen requiring methanogen, Methanobrevibacter smithii), body weight, and percent body fat in a general population cohort. Design and subjects: This was a prospective study (n = 792) of consecutive subjects presenting for breath testing. Setting: The study was conducted at a tertiary care center. Outcome measurements: BMI and percent body fat were measured. Results: Subjects were classified into 4 groups based on breath testing: normal (N) (methane <3 ppm and hydrogen <20 ppm at or before 90 minutes); hydrogen positive only (H+) [methane <3 ppm and hydrogen ≥20 ppm); methane positive only (M+) (methane ≥3 ppm and hydrogen <20 ppm), or methane and hydrogen positive (M+/H+) (methane ≥3 ppm and hydrogen ≥20 ppm]. There were significant differences in age but not in gender across the groups. After controlling for age as a confounding variable, M+/H+ subjects had significantly higher BMI than other groups (N: 24.1 ± 5.2 kg/m(2); H+: 24.2 ± 4.5 kg/m(2); M+: 24.0 ± 3.75 kg/m(2); M+/H+: 26.5 ± 7.1 kg/m(2), P < .02) and also had significantly higher percent body fat (N: 28.3 ± 10.0%; H+: 27.5 ± 9.0%; M+: 28.0 ± 8.9%; M+/H+; 34.1 ± 10.9%, P < .001). Conclusions: The presence of both methane and hydrogen on breath testing is associated with increased BMI and percent body fat in humans. We hypothesize that this is due to colonization with the hydrogen-requiring M smithii, which affects nutrient availability for the host and may contribute to weight gain.

Metano intestinal como biomarcador respiratório para obesidade, pré-diabetes e diabetes mellitus tipo 2

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Jan 2020

Association between breath methane concentration and visceral fat area: A population-based cross-sectional study

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Dec 2019

High visceral fat area (VFA) is a stronger predictor of cardiovascular disease and overall mortality, compared with body mass index (BMI) and waist circumference (WC). Recent reports demonstrate that obesity is related to breath gas, which is produced by the intestinal microflora. However, these studies define obesity using BMI, not VFA. In this population-based cross-sectional study, we investigated the relationship between breath gases (methane and hydrogen) and both VFA and BMI. A total of 1033 participants (62% women; age [mean ± standard deviation] 54.4 ± 14.9 years) in the 2015 Iwaki Health Promotion Project in Japan were enrolled in the study. Breath samples were collected using a breath bag and analyzed by gas chromatography. VFA was measured using a visceral fat meter. The proportion of methanogenic bacteria to total intestinal microbiota was measured by polymerase chain reaction and 16S rRNA gene sequencing analysis. Our analysis revealed a significant association between high VFA and low breath methane, even after adjusting for confounding factors (B=-0.024 and P=0.004). To identify the association between breath methane and VFA in participants with methane-producing bacteria in their intestinal microflora, participants were divided into two groups based on the presence or absence of methanogenic bacteria in their stool. The Methanogen+ group was further divided into two subgroups with breath methane higher (Methane-UP) or lower (Methane-LO) than the median breath methane concentration. VFA was significantly higher in the Methane-UP group than in the Methane-LO group. In participants with methanogenic bacteria, breath methane concentration might be an independent biomarker of visceral fat accumulation.

The safety and sensitivity of a telemetric capsule to monitor gastrointestinal hydrogen production in vivo in healthy subjects: a pilot trial comparison to concurrent breath analysis

Article

Aug 2018
ALIMENT PHARM THER

Background: Intestinal gases are currently used for the diagnosis of disorders including small intestinal bacterial overgrowth and carbohydrate malabsorption. Aim: To compare the performance of measuring hydrogen production within the gut directly with the telemetric gas-sensing capsule with that of indirect measurement through breath testing. Methods: Using standard breath testing protocols, the capsules and breath tests were simultaneously evaluated in a single-blinded trial in 12 healthy subjects. Eight received a single dose of 1.25-40 g inulin and four 20 or 40 g glucose. Safety and reliability of the capsules were also assessed. Results: There were no reported adverse events. All capsules were retrieved and operated without failure. Capsule measurements were in agreement with breath test measurements in magnitude but not in timing; minimal hydrogen production was observed after glucose ingestion and capsule measurements correlated with breath hydrogen after ingestion of 40 g inulin. A dose-dependent increase in concentration of hydrogen was observed from the capsule following ingestion of inulin as low as 1.25 g compared with >10 g for breath measurements. Specifically, the capsule measured >3000 times higher concentrations of hydrogen compared to breath tests, resulting in a signal-to-noise ratio of 23.4 for the capsule compared to 4.2 for the breath test. Conclusions: The capsule showed high sensitivity and signal-to-noise ratio in measuring luminal hydrogen concentrations, provided information on the site of intestinal gas production, and demonstrated safety and reliability. The capsule has potential for improving diagnostic precision for disorders such as small intestinal bacterial overgrowth.

Metabolic signature of C-labeled wheat bran consumption related to gut fermentation in humans: a pilot study

Article

Full-text available

May 2023
EUR J NUTR

Purpose The aim of this pilot study was to analyze concomitantly the kinetics of production of ¹³C-labeled gut-derived metabolites from ¹³C-labeled wheat bran in three biological matrices (breath, plasma, stools), in order to assess differential fermentation profiles among subjects. Methods Six healthy women consumed a controlled breakfast containing ¹³C-labeled wheat bran biscuits. H2, CH4 and ¹³CO2, ¹³CH4 24 h-concentrations in breath were measured, respectively, by gas chromatography (GC) and GC-isotope ratio mass spectrometry (GC-IRMS). Plasma and fecal concentrations of ¹³C-short-chain fatty acids (linear SCFAs: acetate, propionate, butyrate, valerate; branched SCFAs: isobutyrate, isovalerate) were quantified using GC-combustion-IRMS. Gut microbiota composition was assessed by16S rRNA gene sequencing analysis. Results H2 and CH4 24 h-kinetics distinguished two groups in terms of fermentation-related gas excretion: high-CH4 producers vs low-CH4 producers (fasting concentrations: 45.3 ± 13.6 ppm vs 6.5 ± 3.6 ppm). Expired ¹³CH4 was enhanced and prolonged in high-CH4 producers compared to low-CH4 producers. The proportion of plasma and stool ¹³C-butyrate tended to be higher in low-CH4 producers, and inversely for ¹³C-acetate. Plasma branched SCFAs revealed different kinetics of apparition compared to linear SCFAs. Conclusion This pilot study allowed to consider novel procedures for the development of biomarkers revealing dietary fiber-gut microbiota interactions. The non-invasive assessment of exhaled gas following ¹³C-labeled fibers ingestion enabled to decipher distinct fermentation profiles: high-CH4 producers vs low-CH4 producers. The isotope labeling permits a specific in vivo characterisation of the dietary fiber impact consumption on microbiota metabolite production. Clinical trial registration The study has been registered under the number NCT03717311 at ClinicalTrials.gov on October 24, 2018.

Video Capsule Endoscopy and Ingestible Electronics: Emerging Trends in Sensors, Circuits, Materials, Telemetry, Optics, and Rapid Reading Software

Preprint

Full-text available

May 2022

Real-time monitoring of the gastrointestinal tract in a safe and comfortable manner is valuable for the diagnosis and therapy of many diseases. Within this realm, our review captures the trends in ingestible capsule systems with a focus on hardware and software technologies used for capsule endoscopy and remote patient monitoring. We introduce the structure and functions of the gastrointestinal tract, and the FDA guidelines for ingestible wireless telemetric medical devices. We survey the advanced features incorporated in ingestible capsule systems, such as microrobotics, closed-loop feedback, physiological sensing, nerve stimulation, sampling and delivery, panoramic imaging with adaptive frame rates, and rapid reading software. Examples of experimental and commercialized capsule systems are presented with descriptions of their sensors, devices, and circuits for gastrointestinal health monitoring. We also show the recent research in biocompatible materials and batteries, edible electronics, and alternative energy sources for ingestible capsule systems. The results from clinical studies are discussed for the assessment of key performance indicators related to the safety and effectiveness of ingestible capsule procedures. Lastly, the present challenges and outlook are summarized with respect to the risks to health, clinical testing and approval process, and technology adoption by patients and clinicians.

Video Capsule Endoscopy and Ingestible Electronics: Emerging Trends in Sensors, Circuits, Materials, Telemetry, Optics, and Rapid Reading Software

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Nov 2021

Gut Microbiota Interactions With Obesity

Chapter

Jan 2022

The worldwide prevalence of obesity more than doubled between 1980 and 2014. The most frequent cause which leads to the obesity development is a dysbalance between energy intake and energy expenditure. In this complex process genetic susceptibility, environmental and lifestyle factors are involved. Consequently, the gut microbiota is gaining significant research interest in relation to obesity and associated metabolic disorders in an attempt to better understand the etiology of obesity and potentially new methods of its prevention and treatment.

Impact of commonly used drugs on the composition and metabolic function of the gut microbiota

Article

Full-text available

Jan 2020

The human gut microbiota has now been associated with drug responses and efficacy, while chemical compounds present in these drugs can also impact the gut bacteria. However, drug–microbe interactions are still understudied in the clinical context, where polypharmacy and comorbidities co-occur. Here, we report relations between commonly used drugs and the gut microbiome. We performed metagenomics sequencing of faecal samples from a population cohort and two gastrointestinal disease cohorts. Differences between users and non-users were analysed per cohort, followed by a meta-analysis. While 19 of 41 drugs are found to be associated with microbial features, when controlling for the use of multiple medications, proton-pump inhibitors, metformin, antibiotics and laxatives show the strongest associations with the microbiome. We here provide evidence for extensive changes in taxonomy, metabolic potential and resistome in relation to commonly used drugs. This paves the way for future studies and has implications for current microbiome studies by demonstrating the need to correct for multiple drug use. Here, via a metagenomics analysis of population-based and disease cohorts, Vich Vila et al. study the impact of 41 commonly used medications on the taxonomic structures, metabolic potential and resistome of the gut microbiome, underscoring the importance of correcting for multiple drug use in microbiome studies.

Circadian misalignment imposed by nocturnal feeding tends to increase fat deposition in pigs

Article

Nov 2019

Misalignment of day/night and feeding rhythms have been shown to increase fat deposition and the risk for metabolic disorders in humans and rodents. In most studies, however, food intake and intake patterns are not controlled. We studied the effects of circadian misalignment on energy expenditure in pigs in a setting in which we controlled food intake as well as intake patterns. Twelve groups of five male pigs were housed in respiration chambers and fed either during the day (10.00 – 18.00 hours; diurnal feeding: DF) or night (22.00 – 06.00 hours; nocturnal feeding: NF), bihourly the same sequential meals, representing 15, 10, 25, 30 and 20% of the daily allowance. Paired feeding was applied to ensure equal gross energy intake between treatments. Apparent total tract digestibility, energy balances, and heat partitioning were measured, and analysed using a mixed linear model. Apparent total tract energy and dry matter digestibility tended to be lower for NF-pigs than DF-pigs ( P < 0·10). Heat production was 3% lower for NF-pigs than DF-pigs ( P < 0·026) increasing fat retention by 7% in NF-pigs ( P = 0·050). Nocturnal-fed pigs were less active than DF-pigs during the feeding period, but more active during the fasting period. Resting metabolic rate was greater for DF-pigs than NF-pigs during the fasting period. Methane production was 30% greater in NF-pigs than in DF-pigs ( P < 0·001). In conclusion, circadian misalignment has little effect on nutrient digestion, but alters nutrient partitioning, ultimately increasing fat deposition. The causality of the association between circadian misalignment and methane production rates remains to be investigated.

An Overview of the Roles of the Gut Microbiome in Obesity and Diabetes

Chapter

Jan 2018

Archaea from the gut microbiota of humans: Could be linked to chronic diseases?

Article

Aug 2022
ANAEROBE

Archaea comprise a unique domain of organisms with distinct biochemical and genetic differences from bacteria. Methane-forming archaea, methanogens, constitute the predominant group of archaea in the human gut microbiota, with Methanobrevibacter smithii being the most prevalent. However, the effect of methanogenic archaea and their methane production on chronic disease remains controversial. As perturbation of the microbiota is a feature of chronic conditions, such as cardiovascular disease, neurodegenerative diseases and chronic kidney disease, assessing the influence of archaea could provide a new clue to mitigating adverse effects associated with dysbiosis. In this review, we will discuss the putative role of archaea in the gut microbiota in humans and the possible link to chronic diseases.

Direct and Indirect Methods for Studying Human Gut Microbiota

Article

May 2022

Aim: To review the main methods of intestinal microbiota studying. Key points. Currently, molecular genetic methods are used mainly for basic research and do not have a unified protocol for data analysis, which makes it difficult to implement them in clinical practice. Measurement of short chain fatty acids (SCFA) concentrations in plasma provides the data, which can serve as an indirect biomarker of the colonic microbiota composition. However, currently available evidence is insufficient to relate the obtained values (SCFA levels and ratio) to a particular disease with a high degree of certainty. Trimethylamine N-oxide (TMAO) levels in the blood plasma and urine can also reflect the presence of specific bacterial clusters containing genes Cut, CntA/CntB and YeaW/YeaX. Therefore, further studies are required to reveal possible correlations between certain disorders and such parameters as the composition of gut microbiota, dietary patterns and TMAO concentration. Gas biomarkers, i.e. hydrogen, methane and hydrogen sulphide, have been studied in more detail and are better understood as compared to other biomarkers of the gut microbiome composition and functionality. The main advantage of gas biomarkers is that they can be measured multiple times using non-invasive techniques. These measurements provide information on the relative proportion of hydrogenic (i.e. hydrogen producing) and hydrogenotrophic (i.e. methanogenic and sulfate-reducing) microorganisms. In its turn, this opens up the possibility of developing new approaches to correction of individual microbiota components. Conclusions. Integration of the data obtained by gut microbiota studies at the genome, transcriptome and metabolome levels would allow a comprehensive analysis of microbial community function and its interaction with the human organism. This approach may increase our understanding of the pathogenesis of various diseases as well open up new opportunities for prevention and treatment.

Chitin-Glucan Supplementation Altered Gut Microbiota and Improved Postprandial Metabolism in Subjects at Cardiometabolic Risk

Article

Full-text available

Jun 2022

Objectives In this exploratory study, we aimed at characterizing the impact of chitin-glucan (CG), an insoluble dietary fiber, on gut microbiota composition and functions as well as on the cardiometabolic profile in subjects at cardiometabolic risk. Methods Fifteen subjects were included in this double-blind, randomized, twice 3-week cross-over study and consumed 4.5g of CG or maltodextrin (control) as a supplement daily. Before and after the intervention phases, fasting and postprandial metabolic parameters and exhaled gases (hydrogen [H2] and methane [CH4]) were evaluated. Gut microbiota composition (16S next generation sequencing), fecal concentrations of bile acids, long- and short-chain fatty acids (LCFA, SCFA), zonulin, calprotectin and lipopolysaccharide binding protein (LBP) were analyzed. Results Compared to control, CG supplementation increased exhaled H2 following an enriched-fiber breakfast ingestion and decreased postprandial glycemia and triglyceridemia response to a standardized test meal challenge served at lunch. Of note, the decrease in postprandial glycemia was only observed in subjects with higher exhaled H2, assessed upon lactulose breath test performed at inclusion. CG decreased a family belonging to Actinobacteria phylum and increased 3 bacterial taxa: Erysipelotrichaceae UCG.003, Ruminococcaceae UCG.005 and Eubacterium ventriosum group. Fecal metabolites, inflammatory and intestinal permeability markers did not differ between groups. Conclusions We showed that CG supplementation modified the gut microbiota composition and improved postprandial glycemic response, an early determinant of cardiometabolic risk. Our results also suggest breath H2 production as a non-invasive parameter of interest for predicting the effectiveness of dietary fiber intervention. Funding Sources The FiberTAG project was initiated from a European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL). This study was supported by the Service Public de Wallonie. NMD is a recipient of a grant from Belgium National Scientific Research Fund and from UCLouvain. GGM is a recipient of a FSR grant from the UCLouvain.

Chitin-glucan supplementation improved postprandial metabolism and altered gut microbiota in subjects at cardiometabolic risk in a randomized trial

Article

Full-text available

May 2022

Chitin-glucan (CG), an insoluble dietary fiber, has been shown to improve cardiometabolic disorders associated with obesity in mice. Its effects in healthy subjects has recently been studied, revealing its interaction with the gut microbiota. In this double-blind, randomized, cross-over, twice 3-week exploratory study, we investigated the impacts of CG on the cardiometabolic profile and gut microbiota composition and functions in 15 subjects at cardiometabolic risk. They consumed as a supplement 4.5 g of CG daily or maltodextrin as control. Before and after interventions, fasting and postprandial metabolic parameters and exhaled gases (hydrogen [H2] and methane [CH4]) were evaluated. Gut microbiota composition (16S rRNA gene sequencing analysis), fecal concentrations of bile acids, long- and short-chain fatty acids (LCFA, SCFA), zonulin, calprotectin and lipopolysaccharide binding protein (LBP) were analyzed. Compared to control, CG supplementation increased exhaled H2 following an enriched-fiber breakfast ingestion and decreased postprandial glycemia and triglyceridemia response to a standardized test meal challenge served at lunch. Of note, the decrease in postprandial glycemia was only observed in subjects with higher exhaled H2, assessed upon lactulose breath test performed at inclusion. CG decreased a family belonging to Actinobacteria phylum and increased 3 bacterial taxa: Erysipelotrichaceae UCG.003, Ruminococcaceae UCG.005 and Eubacterium ventriosum group. Fecal metabolites, inflammatory and intestinal permeability markers did not differ between groups. In conclusion, we showed that CG supplementation modified the gut microbiota composition and improved postprandial glycemic response, an early determinant of cardiometabolic risk. Our results also suggest breath H2 production as a non-invasive parameter of interest for predicting the effectiveness of dietary fiber intervention.

Human metabolic emissions of carbon dioxide and methane and their implications for carbon emissions

Article

Apr 2022
SCI TOTAL ENVIRON

Carbon dioxide (CO2) and methane (CH4) are important greenhouse gases in the atmosphere and have large impacts on Earth's radiative forcing and climate. Their natural and anthropogenic emissions have often been in focus, while the role of human metabolic emissions has received less attention. In this study, exhaled, dermal and whole-body CO2 and CH4 emission rates from a total of 20 volunteers were quantified under various controlled environmental conditions in a climate chamber. The whole-body CO2 emissions increased with temperature. Individual differences were the most important factor for the whole-body CH4 emissions. Dermal emissions of CO2 and CH4 only contributed ~3.5% and ~5.5% to the whole-body emissions, respectively. Breath measurements conducted on 24 volunteers in a companion study identified one third of the volunteers as CH4 producers (exhaled CH4 exceeded 1 ppm above ambient level). The exhaled CH4 emission rate of these CH4 producers (4.03 ± 0.71 mg/h/person, mean ± one standard deviation) was ten times higher than that of the rest of the volunteers (non-CH4 producers; 0.41 ± 0.45 mg/h/person). With increasing global population and the expected large reduction in global anthropogenic carbon emissions in the next decades, metabolic emissions of CH4 (although not CO2) from humans may play an increasing role in regional and global carbon budgets.

Alterations of the Gut Microbiome Associated to Methane Metabolism in Mexican Children with Obesity

Article

Full-text available

Jan 2022

Gut microbiota is associated with the development of metabolic disorders. To study its association with childhood obesity, we performed a cross-sectional study with 46 children (6–12 years old). We collected fecal samples, food-frequency questionnaires (FFQs), and anthropometric measurements. Shotgun metagenomics were used to obtain the microbial taxonomic diversity and metabolic potential. We identified two dietary profiles characterized by complex carbohydrates and proteins (pattern 1) and saturated fat and simple carbohydrates (pattern 2). We classified each participant into normal weight (NW) or overweight and obese (OWOB) using their body mass index (BMI) z-score. The ratio of Firmicutes/Bacteroidetes and alpha diversity were not different between the BMI groups. Genera contributing to beta diversity between NW and OWOB groups included Bacteroides rodentium, B. intestinalis, B. eggerthii, Methanobrevibacter smithii, Eubacterium sp., and Roseburia sp. B. rodentium was associated with lower BMI and dietary pattern 1 intake. Eubacterium sp. and Roseburia sp. were associated with BMI increments and high consumption of dietary pattern 2. Methane and energy metabolism were found enriched in under-represented KEGG pathways of NW group compared to OWOB. Complex dietary and microbiome interaction leads to metabolic differences during childhood, which should be elucidated to prevent metabolic diseases in adolescence and adulthood.

Chronic Intestinal Pseudo-Obstruction Is Associated with Intestinal Methanogen Overgrowth

Article

Full-text available

Jan 2022
DIGEST DIS SCI

Background Chronic intestinal pseudo-obstruction (CIP) is a rare motility disorder characterized by dilated small bowel in the absence of mechanical obstruction. CIP has a known association with small intestinal bacterial overgrowth (SIBO); however, data regarding association with specific subtypes such as methane-positive (M+) and hydrogen-positive (H+) SIBO are limited. Therefore, we conducted this study to characterize subtypes of SIBO in CIP and compare them with non-CIP patients. Aims The aim is to explore the association and prevalence of hydrogen and methane subtypes of SIBO in patients with CIP. Methods A retrospective chart review was conducted for 494 patients who underwent glucose breath tests (GBT) in 2019. CIP was diagnosed based on clinical suspicion and after ruling out mechanical obstruction. We also reviewed demographic data, including age, gender, body mass index, tobacco and alcohol history, medical comorbidities, use of proton pump inhibitors, and history of colectomy. Results Among 494 patients, 7.7% (38) had CIP. The prevalence of M+ GBT in CIP patients was higher compared with non-CIP patients, and it was significant [52.6% (20/38) versus 11.8% (54/456), p < 0.001]. The prevalence of H+ GBT in our cohort of CIP patients was similar to that of non-CIP patients [23.7% (9/38) versus 25.7% (117/456), p = 0.941]. Conclusion The prevalence of methane-positive GBT was higher in CIP patients than in patients without CIP. This finding further strengthens the hypothesis that the relationship between motility disorders and methanogen overgrowth is facilitative.

Small Intestinal Bacterial Overgrowth in Subclinical Hypothyroidism of Pregnant Women

Article

Full-text available

May 2021

Objective To evaluate the small intestinal bacterial overgrowth (SIBO) of subclinical hypothyroidism of pregnant women, and explore their possible relevance. Methods In total, 224 pregnant women with subclinical hypothyroidism during pregnancy (study group) and 196 pregnant women whose thyroid function was normal (control group) were enrolled in this study. Lactulose-based hydrogen and methane breath test was performed to evaluate the growth of intestinal bacteria. The serum-free thyroid hormone (FT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), body mass index (BMI) and gastrointestinal symptoms were detected and recorded. Results The positive rates of SIBO were 56.7% and 31.6% in study group and control group, respectively. The levels of C response protein (CRP), abdominal distension and constipation in study group were higher than those in the control group. The risk of abdominal distension and constipation in SIBO-positive pregnant women were higher than that in SIBO-negative pregnant women, and the BMI of SIBO-positive patients in the two groups was lower than that of SIBO-negative patients in each group. In addition, the TPOAb-positive rate and TSH levels were higher but the FT4 level was lower in SIBO-positive patients compared to SIBO-negative patients in study group. Conclusion The occurrence of subclinical hypothyroidism is related to SIBO, and the excessive growth of small intestinal bacteria may affect gastrointestinal symptoms. Clinical Trial http://www.chictr.org.cn/index.aspx , identifier ChiCTR1900026326.

Seasonal shifts in the gut microbiome indicate plastic responses to diet in wild geladas

Article

Full-text available

Jan 2021

Background Adaptive shifts in gut microbiome composition are one route by which animals adapt to seasonal changes in food availability and diet. However, outside of dietary shifts, other potential environmental drivers of gut microbial composition have rarely been investigated, particularly in organisms living in their natural environments. Results Here, we generated the largest wild nonhuman primate gut microbiome dataset to date to identify the environmental drivers of gut microbial diversity and function in 758 samples collected from wild Ethiopian geladas ( Theropithecus gelada ). Because geladas live in a cold, high-altitude environment and have a low-quality grass-based diet, they face extreme thermoregulatory and energetic constraints. We tested how proxies of food availability (rainfall) and thermoregulatory stress (temperature) predicted gut microbiome composition of geladas. The gelada gut microbiome composition covaried with rainfall and temperature in a pattern that suggests distinct responses to dietary and thermoregulatory challenges. Microbial changes were driven by differences in the main components of the diet across seasons: in rainier periods, the gut was dominated by cellulolytic/fermentative bacteria that specialized in digesting grass, while during dry periods the gut was dominated by bacteria that break down starches found in underground plant parts. Temperature had a comparatively smaller, but detectable, effect on the gut microbiome. During cold and dry periods, bacterial genes involved in energy, amino acid, and lipid metabolism increased, suggesting a stimulation of fermentation activity in the gut when thermoregulatory and nutritional stress co-occurred, and potentially helping geladas to maintain energy balance during challenging periods. Conclusion Together, these results shed light on the extent to which gut microbiota plasticity provides dietary and metabolic flexibility to the host, and might be a key factor to thriving in changing environments. On a longer evolutionary timescale, such metabolic flexibility provided by the gut microbiome may have also allowed members of Theropithecus to adopt a specialized diet, and colonize new high-altitude grassland habitats in East Africa.

Regional distribution of Christensenellaceae and its associations with metabolic syndrome based on a population-level analysis

Article

Full-text available

Aug 2020

The link between the gut microbiota and metabolic syndrome (MetS) has attracted widespread attention. Christensenellaceae was recently described as an important player in human health, while its distribution and relationship with MetS in Chinese population is still unknown. This study sought to observe the association between Christensenellaceae and metabolic indexes in a large sample of residents in South China. A total of 4,781 people from the GGMP project were included, and the fecal microbiota composition of these individuals was characterized by 16S rRNA sequencing and analyzed the relation between Christensenellaceae and metabolism using QIIME (Quantitative Insight Into Microbial Ecology, Version 1.9.1). The results demonstrated that microbial richness and diversity were increased in the group with a high abundance of Christensenellaceae , who showed a greater complexity of the co-occurrence network with other bacteria than residents who lacked Christensenellaceae . The enriched bacterial taxa were predominantly represented by Oscillospira , Ruminococcaceae , RF39 , Rikenellaceae and Akkermansia as the Christensenellaceae abundance increased, while the abundances of Veillonella , Fusobacterium and Klebsiella were significantly reduced. Furthermore, Christensenellaceae was negatively correlated with the pathological features of MetS, such as obesity, hypertriglyceridemia and body mass index (BMI). We found reduced levels of lipid biosynthesis and energy metabolism pathways in people with a high abundance of Christensenellaceae , which may explain the negative relationship between body weight and Christensenellaceae . In conclusion, we found a negative correlation between Christensenellaceae and MetS in a large Chinese population and reported the geographical distribution of Christensenellaceae in the GGMP study. The association data from this population-level research support the investigation of strains within Christensenellaceae as potentially beneficial gut microbes.

Metabolic Dysfunction and Asthma: Current Perspectives

Article

Full-text available

Jul 2020

Helena Pite,1,2 Laura Aguiar,1 Judit Morello,2 Emília C Monteiro,2 Ana Catarina Alves,3,4 Mafalda Bourbon,3,4 Mário Morais-Almeida1 1Allergy Center, CUF Infante Santo Hospital/CUF Descobertas Hospital, Lisbon, Portugal; 2CEDOC, Chronic Diseases Research Center, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal; 3Department of Health Promotion and Chronic Diseases, National Institute of Health Doutor Ricardo Jorge, Lisbon, Portugal; 4Biosystems and Integrative Sciences Institute (BioISI), Faculty of Sciences, University of Lisbon, Lisbon, PortugalCorrespondence: Helena PiteAllergy Center, CUF-Descobertas Hospital, Rua Mário Botas, Lisbon 1998-018, PortugalTel +351962790162Fax +351210025220Email helenampite@gmail.comAbstract: The increasing knowledge of the mechanisms involved in metabolism is shifting the paradigms by which the pathophysiology of many pulmonary diseases is understood. Metabolic dysfunction is recognized in obesity-associated asthma, but other metabolic conditions have been shown to be independently related to asthma. Novel insights have also recently been brought by metabolomics in this filed. The purpose of this review is to discuss current perspectives regarding metabolic dysfunction in asthma, from obesity-related asthma to other metabolic conditions and the role of current pharmacological therapeutic strategies and lifestyle interventions. Obesity is a well-recognized risk factor for asthma across the lifespan, which is generally associated with poorer response to current available treatments, rendering a more severe, refractory disease status. Besides the epidemiological and clinical link, untargeted metabolomics studies have recently supported the obesity-associated asthma phenotype at the molecular level. Not only obesity-related, but also other aspects of metabolic dysregulation can be independently linked to asthma. These include hyperinsulinemia, dyslipidemia and hypertension, which need to be taken into account, even in the non-obese patient. Untargeted metabolomics studies have further highlighted several other metabolic pathways that can be altered in asthma, namely regarding oxidative stress and systemic inflammation, and also suggesting the importance of microbiota in asthma pathogenesis. Considering the reduced response to corticosteroids, other pharmacologic treatments have been shown to be effective regardless of body mass index. Non-pharmacologic treatments (namely weight reduction and dietary changes) may bring substantial benefit to the asthmatic patient. Taken together, this evidence points towards the need to improve our knowledge in this filed and, in particular, to address the influence of environmental factors in metabolic dysfunction and asthma development. Personalized medicine is definitely needed to optimize treatment, including a holistic view of the asthmatic patient in order to set accurate pharmacologic therapy together with dietary, physical exercise and lifestyle interventions.Keywords: asthma, diet, inflammation, metabolic, metabolomics, obesity

Influencing Factors on Lactulose Breath Test Results

Article

Full-text available

Jan 2020

Background/aims: This study aimed to identify the demographic and clinical factors associated with positive breath-test results and to assess the relationship between hydrogen and methane production in patients with suspected irritable bowel syndrome (IBS). Methods: The demographic and clinical factors of 268 patients with suspected IBS, who had undergone a lactulose breath test, were analyzed. Results: Of 268 patients included in this study, 143 (53.4%) were females. The median age and BMI of the patients was 58.0 years (range, 18.0-80.0 years) and 22.5 kg/m2 (range, 14.4-34.3 kg/m2), respectively. A weak positive correlation was observed between the BMI and baseline hydrogen level (rho=0.134, p=0.031). Women were significantly more likely to show a ≥20 ppm increase in hydrogen within 90 min (early hydrogen increase, p=0.049), a ≥10 ppm increase in methane within 90 min (early methane increase, p=0.001), and a ≥10 ppm increase in methane between 90 min and 180 min (late methane increase, p=0.002) compared to men. The baseline hydrogen level was related to the baseline methane level (rho=0.592, p<0.001) and the maximal hydrogen level within 90 min was related to maximal methane level within 90 min (rho=0.721, p<0.001). Patients with an early hydrogen increase (43.8%) were more likely to show a positive result for an early methane increase compared to patients without an early increase in hydrogen (0%, p<0.001). Conclusions: Women were associated with high rates of positive lactulose breath-test results. In addition, methane production was correlated with hydrogen production.

Culture of Methanogenic Archaea from Human Colostrum and Milk

Article

Full-text available

Dec 2019

Archaeal sequences have been detected in human colostrum and milk, but no studies have determined whether living archaea are present in either of these fluids. Methanogenic archaea are neglected since they are not detected by usual molecular and culture methods. By using improved DNA detection protocols and microbial culture techniques associated with antioxidants previously developed in our center, we investigated the presence of methanogenic archaea using culture and specific Methanobrevibacter smithii and Methanobrevibacter oralis real-time PCR in human colostrum and milk. M. smithii was isolated from 3 colostrum and 5 milk (day 10) samples. M. oralis was isolated from 1 milk sample. For 2 strains, the genome was sequenced, and the rhizome was similar to that of strains previously isolated from the human mouth and gut. M. smithii was detected in the colostrum or milk of 5/13 (38%) and 37/127 (29%) mothers by culture and qPCR, respectively. The different distribution of maternal body mass index according to the detection of M. smithii suggested an association with maternal metabolic phenotype. M. oralis was not detected by molecular methods. Our results suggest that breastfeeding may contribute to the vertical transmission of these microorganisms and may be essential to seed the infant’s microbiota with these neglected critical commensals from the first hour of life.

Methane and Inflammation - A Review (Fight Fire with Fire)

Article

Full-text available

Dec 2019

Mammalian methanogenesis is regarded as an indicator of carbohydrate fermentation by anaerobic gastrointestinal flora. Once generated by microbes or released by a non-bacterial process, methane is generally considered to be biologically inactive. However, recent studies have provided evidence for methane bioactivity in various in vivo settings. The administration of methane either in gas form or solutions has been shown to have anti-inflammatory and neuroprotective effects in an array of experimental conditions, such as ischemia/reperfusion, endotoxemia and sepsis. It has also been demonstrated that exogenous methane influences the key regulatory mechanisms and cellular signalling pathways involved in oxidative and nitrosative stress responses. This review offers an insight into the latest findings on the multi-faceted organ protective activity of exogenous methane treatments with special emphasis on its versatile effects demonstrated in sepsis models.

Is the delivery mode a critical factor for the microbial communities in the meconium?

Article

Full-text available

Nov 2019

Background: Mothers are the primary source of bacteria for newborns, but it is unclear whether mother-to-newborn transmission occurs prior to, during or after birth. Similarly, the effect of the delivery mode on neonatal microorganisms has been the focus of controversy. Methods: Healthy maternal and neonatal pairs that underwent vaginal birth and caesarean section were enrolled in this study. Meconium, placenta, membrane and amniotic fluid samples for newborns and vaginal, rectal and oral samples for mothers were collected. All samples were amplified and sequenced by a 16S rRNA gene primer set targeting bacteria and archaea. Findings: A total of 550 samples from 36 mother-neonate pairs with vaginal births and 42 mother-neonate pairs with caesarean sections were included in this study. The negative controls showed that the data analysis in this study was not affected by contamination. There was a high diversity of microbial communities in the pregnancy environment of the foetus. Meconium samples could be divided into three distinct types that were not influenced by the delivery method. Interpretation: The distribution patterns of bacterial communities in the meconium, placenta, and foetal membranes were highly similar and had nothing to do with the mode of delivery. For approximately half of the placental microorganisms, the same sequence could be found in the vaginal, rectal, and oral samples of the mother.

Risk Factors for Asymptomatic Colon Diverticulosis

Article

Full-text available

Sep 2019

Backgrounds/aims: The etiology of colon diverticulosis is related to a range of genetic, biological, and environmental factors, but the risk factors for asymptomatic diverticulosis of the colon are unclear. This study examined the risk factors for asymptomatic colon diverticulosis. Methods: This retrospective study included examinees who underwent a colonoscopy for screening at the health check-up center of SAM Hospital between January 2016 and December 2016. The examinees with colon diverticulosis found by colonoscopy were compared with those without diverticulosis. The comparison factors were age, gender, alcohol consumption, smoking status, medical history, lipid profile, body mass index, visceral fat area, waist-hip ratio, and severity of a fatty liver. Results: This study included 937 examinees and the overall prevalence of diverticulosis was 8.1% (76/937). Fatty liver was found in 69.7% (53/76) in cases of colon diverticulosis and 50.3% (433/861) in the control group (p=0.001). The average waist-hip ratio was 0.92±0.051 in colon diverticulosis and 0.90±0.052 in the control group (p=0.052). Multivariate analysis revealed the waist-hip ratio (OR=1.035, 95% CI 1.000-1.070, p=0.043), moderate fatty liver (OR=2.238, 95% CI 1.026-4.882, p=0.043), and severe fatty liver (OR=5.519, 95% CI 1.236-21.803, p=0.025) to be associated with an increased risk of asymptomatic colon diverticulosis. Conclusions: The waist-hip ratio, moderate fatty liver, and severe fatty liver are risk factors for asymptomatic colon diverticulosis. Central obesity, which can be estimated by the waist-hip ratio, and fatty liver might affect the pathogenesis of asymptomatic colon diverticulosis.

Diet-Independent Correlations between Bacteria and Dysfunction of Gut, Adipose Tissue, and Liver: A Comprehensive Microbiota Analysis in Feces and Mucosa of the Ileum and Colon in Obese Mice with NAFLD

Article

Full-text available

Dec 2018
INT J MOL SCI

Development of non-alcoholic fatty liver disease (NAFLD) is linked to obesity, adipose tissue inflammation, and gut dysfunction, all of which depend on diet. So far, studies have mainly focused on diet-related fecal microbiota changes, but other compartments may be more informative on host health. We present a first systematic analysis of microbiota changes in the ileum and colon using multiple diets and investigating both fecal and mucosal samples. Ldlr−/−.Leiden mice received one of three different energy-dense (ED)-diets (n = 15/group) for 15 weeks. All of the ED diets induced obesity and metabolic risk factors, altered short-chain fatty acids (SCFA), and increased gut permeability and NAFLD to various extents. ED diets reduced the diversity of high-abundant bacteria and increased the diversity of low-abundant bacteria in all of the gut compartments. The ED groups showed highly variable, partially overlapping microbiota compositions that differed significantly from chow. Correlation analyses demonstrated that (1) specific groups of bacteria correlate with metabolic risk factors, organ dysfunction, and NAFLD endpoints, (2) colon mucosa had greater predictive value than other compartments, (3) correlating bacteria differed per compartment, and (4) some bacteria correlated with plasma SCFA levels. In conclusion, this comprehensive microbiota analysis demonstrates correlations between the microbiota and dysfunctions of gut, adipose tissue, and liver, independent of a specific disease-inducing diet.

The human archaeome: Methodological pitfalls and knowledge gaps

Article

Dec 2018

Forty years ago, archaea were described as a separate domain of life, distinct from bacteria and eukarya. Although it is known for quite a long time that methanogenic archaea are substantial components of the human gastrointestinal tract (GIT) and the oral cavity, the knowledge on the human archaeome is very limited. Various methodological problems contribute to the invisibility of the human archaeome, resulting in severe knowledge gaps and contradictory information. Similar to the bacteriome, the archaeal biogeography was found to be site-specific, forming (i) the thaumarchaeal skin landscape, (ii) the (methano)euryarchaeal GIT landscape, (iii) a mixed skin/GIT landscape in nose, and (iv) a woesearchaeal lung landscape, including numerous unknown archaeal clades. Compared with so-called universal microbiome approaches, archaea-specific protocols reveal a wide diversity and high quantity of archaeal signatures in various human tissues, with up to 1 : 1 ratios of bacteria and archaea in appendix and nose samples. The archaeome interacts closely with the bacteriome and the human body cells, whereas the roles of the human-associated archaea with respect to human health are only sparsely described. Methanogenic archaea and methane production were correlated with many health issues, including constipation, periodontitis and multiple sclerosis. However, one of the most burning questions — do archaeal pathogens exist? — still remains obscure to date.

The physiologic and phenotypic significance of variation in human amylase gene copy number

Article

Sep 2018
AM J CLIN NUTR

Background: Salivary α-amylase gene (AMY1) copy number (CN) correlates with the amount of salivary α-amylase, but beyond this, the physiologic significance is uncertain. Objective: We hypothesized that individuals with higher AMY1 CN would digest starchy foods faster and show higher postprandial responses and lower breath hydrogen excretion compared with those with low CN. Design: Four linked studies were conducted. In Study 1, we genotyped 201 healthy subjects with the use of real-time quantitative polymerase chain reaction and determined glucose tolerance, insulin sensitivity, salivary α-amylase activity, body mass index (BMI), and macronutrient intake. In Study 2, a pool of 114 subjects tested 6 starchy foods, 3 sugary foods, 1 mixed meal, and 2 reference glucose solutions, containing either 50 or 25 g of available carbohydrate. In Study 3, we compared glycemic and insulin responses to starchy foods with responses to glucose in 40 individuals at extremes of high and low CN. In Study 4, we compared breath hydrogen and methane responses over 8 h in 30 individuals at extremes of CN. Results: AMY1 CN correlated positively with salivary α-amylase activity (r = 0.62, P < 0.0001, n = 201) but not with BMI, glucose tolerance, or insulin sensitivity. However, CN was strongly correlated with normalized glycemic responses to all starchy foods (explaining 26-61% of interindividual variation), but not to sucrose or fruit. Individuals in the highest compared with the lowest decile of CN produced modestly higher glycemia (+15%, P = 0.018), but not insulinemia, after consuming 2 starchy foods. Low-CN individuals displayed >6-fold higher breath methane levels in the fasting state and after starch ingestion than high-CN individuals (P = 0.001), whereas hydrogen excretion was similar. Conclusions: Starchy foods are digested faster and produce higher postprandial glycemia in individuals with high AMY1 CN. In contrast, having low CN is associated with colonic methane production. This trial was registered at www.anzctr.org.au as ACTRN12617000670370.

A taxonomic signature of obesity in a large study of American adults

Article

Full-text available

Jun 2018

Animal models suggest that gut microbiota contribute to obesity; however, a consistent taxonomic signature of obesity has yet to be identified in humans. We examined whether a taxonomic signature of obesity is present across two independent study populations. We assessed gut microbiome from stool for 599 adults, by 16S rRNA gene sequencing. We compared gut microbiome diversity, overall composition, and individual taxon abundance for obese (BMI ≥ 30 kg/m2), overweight (25 ≤ BMI < 30), and healthy-weight participants (18.5 ≤ BMI < 25). We found that gut species richness was reduced (p = 0.04), and overall composition altered (p = 0.04), in obese (but not overweight) compared to healthy-weight participants. Obesity was characterized by increased abundance of class Bacilli and its families Streptococcaceae and Lactobacillaceae, and decreased abundance of several groups within class Clostridia, including Christensenellaceae, Clostridiaceae, and Dehalobacteriaceae (q < 0.05). These findings were consistent across two independent study populations. When random forest models were trained on one population and tested on the other as well as a previously published dataset, accuracy of obesity prediction was good (~70%). Our large study identified a strong and consistent taxonomic signature of obesity. Though our study is cross-sectional and causality cannot be determined, identification of microbes associated with obesity can potentially provide targets for obesity prevention and treatment.

Obesity and the Risk of Colonic Diverticulosis: A Meta-analysis

Article

Apr 2018
DIS COLON RECTUM

Background: The possible relationship between obesity and the risk of colonic diverticulosis has been suggested by recent epidemiologic studies, although the results were inconsistent. Objective: This systematic review and meta-analysis was conducted to summarize all of the available data. Data sources: A comprehensive literature review was conducted using the MEDLINE and EMBASE databases through January 2017. Study selection: Studies that compared the risk of colonic diverticulosis among subjects with obesity versus those without obesity were included. Main outcome measures: Effect estimates from each study were extracted and combined together using a random-effect, generic inverse variance method. Results: Of 2989 potentially eligible articles, 10 studies (9 cross-sectional studies and 1 prospective cohort study) with 53,520 participants met the eligibility criteria and were included in the meta-analysis. The risk of colonic diverticulosis in obese subjects was significantly higher than in those without obesity, with a pooled OR of 1.41 (95% CI, 1.20-1.65). The statistical heterogeneity was high, with an I of 75%. Limitations: High statistical heterogeneity and publication bias in favor of positive studies may have been present in this meta-analysis. Conclusions: A significant association between colonic diverticulosis and obesity was shown in this study. However, additional studies are still required to determine the causality. See Video Abstract at http://links.lww.com/DCR/A500.

The Role of Small Intestinal Bacterial Overgrowth in Obesity and Its Related Diseases

Article

Apr 2023
BIOCHEM PHARMACOL

Obesity has become a major public health problem worldwide and its occurrence is increasing globally. Obesity has also been shown to be involved in the occurrence and development of many diseases and pathological conditions, such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM), insulin resistance (IR). In recent years, gut microbiota has received extensive attention as an important regulatory part involved in host diseases and health status. A growing body of evidence suggests that gut microbiota dysbiosis has a significant adverse effect on the host. Small intestinal bacterial overgrowth (SIBO), a type of intestinal microbial dysbiosis, has been gradually revealed to be associated with obesity and its related diseases. The presence of SIBO may lead to the destruction of intestinal barrier integrity, increased intestinal permeability, increased endotoxin levels, activation of inflammatory responses, and translocation of bacteria from the colon to the small intestine. However, the causal relationship between SIBO and obesity and the specific mechanisms have not been well elucidated. This review discusses the cross-talk between SIBO and obesity and its related diseases, and expounds its potential mechanisms and interventions, which may help to discover new therapeutic targets for obesity and its related diseases and develop treatment options.

Microbiome and Obesity

Chapter

Feb 2023

Obesity is a complex metabolic disease disturbing both children and adults. Childhood obesity is a consequence of developing this pathology and associated conditions in adulthood. The disbalance/imbalance between energy expenditure and intake is the most frequent cause of overweight. Genetic susceptibility, inflammation and environmental and/or lifestyle factors may be involved in this complicated process. Modern research suggests that the microbiome plays a significant role in the pathophysiology of obesity. As a result, the gut microbiota is gaining meaningful scientific interest concerning obesity and different associated metabolic disorders to understand obesity’s etiologyObesity better and find modern methods of its prevention and/or treatment. This review presents personalized medicinePersonalized medicine as a modern approach to the preventionPrevention and treatmentTreatments of obesityObesity. First, we review obesityObesity as a diseaseDiseases of civilization with complex health issuesHealth issues (unhealthy nutritionUnhealthy nutrition, psychosocial, behavioral, environmental, epigenetic and genetic/genomic risk factorsGenetic/genomic risk factors). Second, the relationship between obesityObesity and gut microbiotaGut microbiota has been presented in the context of predictive, preventive, and personalized (PPPM/3P) medicine. Finally, we discuss that pre and/or probiotic therapyProbiotic therapies is considered the promising strategy for control of metabolic disordersMetabolic disorders by virtue of microbiota compositionMicrobiota compositions and/or health maintenanceHealth maintenancerecoveryRecovery in personalized medicinePersonalized medicine and could be additional development and standardization of innovative targeted therapiesInnovative targeted therapies and clinical tools.

2.10 - Medication and Health Risks Associated With Neglected Side Effects on Gut Microbiota

Chapter

Aug 2022

It is well-known that the use of antibiotics, probiotics, and fecal microbiota transplantation (FMT) modulate gut microbiota, including favoring specific structures and functions or restoring the impaired microbiome. Although manipulation of the gut microbiome is attractive in the prevention and treatment of some associated diseases, there are some medications with surprisingly harmful effects on the gut microbiota composition and diversity. Furthermore, based on data published, by exerting such detrimental effects on the gut ecosystem, some commonly used drugs such as proton pump inhibitors, laxatives, antidiabetic, cardiovascular drugs, psychotropics, anticancer drugs are associated with significant health risks for the patients.

Highly Sensitive and Selective Detection of Hydrogen Using Pd-Coated SnO2 Nanorod Arrays for Breath-Analyzer Applications

Article

Full-text available

Mar 2022
SENSORS-BASEL

We report a breath hydrogen analyzer based on Pd-coated SnO2 nanorods (Pd-SnO2 NRs) sensor integrated into a miniaturized gas chromatography (GC) column. The device can measure a wide range of hydrogen (1–100 ppm), within 100 s, using a small volume of human breath (1 mL) without pre-concentration. Especially, the mini-GC integrated with Pd-SnO2 NRs can detect 1 ppm of H2, as a lower detection limit, at a low operating temperature of 152 °C. Furthermore, when the breath hydrogen analyzer was exposed to a mixture of interfering gases, such as carbon dioxide, nitrogen, methane, and acetone, it was found to be capable of selectively detecting only H2. We found that the Pd-SnO2 NRs were superior to other semiconducting metal oxides that lack selectivity in H2 detection. Our study reveals that the Pd-SnO2 NRs integrated into the mini-GC device can be utilized in breath hydrogen analyzers to rapidly and accurately detect hydrogen due to its high selectivity and sensitivity.

Prevalence of methanogens and associated factors in patients with irritable bowel syndrome and healthy controls in a Southeastern Mexican population

Article

Dec 2021

Introduction Methane (CH4) is an inert gas produced by colonic anaerobes and has been associated with different intestinal diseases, including irritable bowel syndrome (IBS). According to geographic region, the prevalence of methanogens varies, being higher in Africa (80%) and lower in the United States (35-40%). In Mexico, the prevalence of methanogens is unknown. Aim To evaluate the prevalence of CH4 producers and associated factors in a group of patients with IBS and controls in a Mexican population. Materials and methods A baseline fasting measurement of alveolar H2 and CH4 gas was carried out, by gas chromatography (stationary phase), in consecutive patients diagnosed with IBS and a control group. Subjects with baseline levels of H2 of 0 ppm and CH4 ≥ 5 ppm were classified as methanogenic. Results A total of 132 controls (53.8% women) and 67 patients with IBS (76% women) were included. The overall prevalence (n = 199) of methanogenic subjects was 38% (n = 76) (95% CI: 0.31-0.45) and they had a greater prevalence of overweight/obesity (56.5 vs 39.8%, P = .028). The prevalence of methanogens in the healthy controls was 41.6% (95% CI: 0.33-0.49), whereas, in the patients with IBS, it was 31.4% (n = 21, 71% IBS-C and 29% IBS-M). Conclusions The prevalence of methanogens in our study on a Mexican population was comparable to that reported in other populations and was associated with overweight/obesity. One-third of the patients with IBS presented with methanogens. Said microorganisms were particularlyassociated with the constipation-predominant IBS subtype.

Prevalencia de metanógenos y factores asociados en pacientes con síndrome de intestino irritable y controles sanos en una población del sureste de México

Article

Oct 2021

Resumen Introducción El metano (CH4) es un gas inerte producido por anaerobios colónicos y se ha asociado a diferentes patologías intestinales, incluyendo el síndrome de intestino irritable (SII). De acuerdo con la región geográfica la prevalencia de metanógenos es variable, siendo mayor en África (80%) y menor en Estados Unidos (35-40%). En México se desconoce cuál es la prevalencia de metanógenos. Objetivo Evaluar la prevalencia de productores de CH4 y los factores asociados en un grupo de pacientes con SII y controles en población mexicana. Material y métodos Se realizó de forma basal la medición en ayuno de gas alveolar de H2 y CH4 a través de cromatografía de gases estacionaria a pacientes consecutivos con diagnóstico de SII y un grupo control. Se clasificaron como metanógenos los sujetos con niveles basales de H2 de 0 ppm y CH4 ≥ 5 ppm. Resultados Se incluyeron 132 controles (53.8% mujeres) y 67 pacientes con SII (76% mujeres). De forma global (n = 199), la prevalencia de metanógenos fue del 38% (n = 76) (IC 95%: 0.31-0.45). Los sujetos metanógenos tuvieron mayor prevalencia de sobrepeso/obesidad (56.5 vs 39.8%, p = 0.028). La prevalencia de metanógenos en controles sanos fue del 41.6% (IC 95%: 0.33-0.49), mientras que en los pacientes con SII fue del 31.4% (n = 21, 71% SII-E y 29% SII-M). Conclusiones La prevalencia de metanógenos en México es comparable con lo reportado en otras poblaciones y se asoció con sobrepeso/obesidad. Una tercera parte de los pacientes con SII son metanógenos, y esto se asoció en especial con el subtipo estreñimiento.

IBS in overweight and obese individuals: a new disease phenotype?

Article

Jan 2021

Bacteria and Methanogens in the Human Microbiome: a Review of Syntrophic Interactions

Article

Full-text available

Jun 2021
MICROB ECOL

Methanogens are microorganisms belonging to the Archaea domain and represent the primary source of biotic methane. Methanogens encode a series of enzymes which can convert secondary substrates into methane following three major methanogenesis pathways. Initially recognized as environmental microorganisms, methanogens have more recently been acknowledged as host-associated microorganisms after their detection and initial isolation in ruminants in the 1950s. Methanogens have also been co-detected with bacteria in various pathological situations, bringing their role as pathogens into question. Here, we review reported associations between methanogens and bacteria in physiological and pathological situations in order to understand the metabolic interactions explaining these associations. To do so, we describe the origin of the metabolites used for methanogenesis and highlight the central role of methanogens in the syntrophic process during carbon cycling. We then focus on the metabolic abilities of co-detected bacterial species described in the literature and infer from their genomes the probable mechanisms of their association with methanogens. The syntrophic interactions between bacteria and methanogens are paramount to gut homeostasis. Therefore, any dysbiosis affecting methanogens might impact human health. Thus, the monitoring of methanogens may be used as a bio-indicator of dysbiosis. Moreover, new therapeutic approaches can be developed based on their administration as probiotics. We thus insist on the importance of investigating methanogens in clinical microbiology.

Bovine host genome acts on specific metabolism, communication and genetic processes of rumen microbes host-genomically linked to methane emissions

Preprint

Full-text available

Mar 2021

Whereas recent studies in different species showed that the host genome shapes the microbial community profile, our new research strategy revealed substantial host genomic control of comprehensive functional microbial processes in the rumen of bovines by utilising microbial gene profiles from whole metagenomic sequencing. Of 1,107/225/1,141 rumen microbial genera/metagenome assembled uncultured genomes (RUGs)/genes identified, 203/16/352 were significantly (P<2.02 x10-5) heritable (0.13 to 0.61), revealing substantial variation in host genomic control. We found 29/22/115 microbial genera/RUGs/genes host-genomically correlated (-0.93 to 0.92) with emissions of the potent greenhouse gas methane (CH4), highlighting the strength of host genomic control of specific microbial processes impacting on CH4. Only one of these microbial genes was directly involved in methanogenesis (cofG), whereas others were involved in providing substrates for archaea (e.g. bcd and pccB), important microbial interspecies communication mechanisms (ABC.PE.P), host-microbiome interaction (TSTA3) and genetic information processes (RP-L35). In our population, selection based on abundances of the 30 most informative microbial genes provided a mitigation potential of 17% of mean CH4 emissions per generation, which is higher than for selection based on measured CH4 using respiration chambers (13%), indicating the high potential of microbiome-driven breeding to cumulatively reduce CH4 emissions and mitigate climate change.

Chickpea Extract Ameliorates Metabolic Syndrome Symptoms via Restoring Intestinal Ecology and Metabolic Profile in Type 2 Diabetic Rats

Article

May 2021

Scope Chickpeas have been recognized as a natural Uyghur medicine in Xinjiang (China) for 2500 years. Although the phenotypic effect on obesity or diabetes was authenticated, the mechanism was unclear. This work aimed to study the effect of chickpea extract (CE) on metabolic syndrome induced by type 2 diabetes and to reveal its related mechanisms, focusing on intestinal flora and metabolomics. Methods and results Diabetic rats were induced by a high‐fat diet and intraperitoneal injection of streptozotocin. CE supplementation (10 g/kg) for 4 weeks improved the hyperglycaemia, inflammatory state, and organ functions of diabetic rats. The metabolic profile trajectories of urine and faeces obtained by NMR had good separations among all groups, and CE significantly increased the contents of SCFAs in the cecum. Moreover, CE relieved intestinal dysbiosis by increasing the abundance of SCFAs‐producing bacteria (e.g., Enterococcaceae) but reducing conditional pathogenic bacteria (e.g., Corynebacterium). PICRUSt predicted the functions of gut microbiome from the 16S rRNA gene sequences and metagenome, and found that CE restored amino acids degradation, bile acids metabolism and carbohydrate metabolism. Conclusion This study elucidated the role of CE from the perspective of metabolomics and the microbiota, which provided evidence for chickpea as a prebiotic to prevent diabetes. This article is protected by copyright. All rights reserved

Emerging wearable technology applications in gastroenterology: A review of the literature

Article

Full-text available

Mar 2021
WORLD J GASTROENTERO

Benjamin Woo

The field of gastroenterology has recently seen a surge in wearable technology to monitor physical activity, sleep quality, pain, and even gut activity. The past decade has seen the emergence of wearable devices including Fitbit, Apple Watch, AbStats, and ingestible sensors. In this review, we discuss current and future devices designed to measure sweat biomarkers, steps taken, sleep efficiency, gastric electrical activity, stomach pH, and intestinal contents. We also summarize several clinical studies to better understand wearable devices so that we may assess their potential benefit in improving healthcare while also weighing the challenges that must be addressed. Core Tip: Wearable technology allows continuous health monitoring to provide a novel means of diagnosing and managing patients. Applications of wearable technology such as wrist wearables, abdominal wearables, smartphones and mobile apps, and ingestible sensors, are developing in gastroenterology. The aim of this review is to investigate current data from the literature that studies recent wearable technologies in several gastrointestinal diseases including inflammatory bowel disease, irritable bowel syndrome, and other functional gastrointestinal disorders. Chong KPL et al. Wearable technology applications in gastroenterology WJG https://www.wjgnet.com 1150

Nutrient yield from starch in pigs: Consequences for energy balance and meal patterns

Thesis

Full-text available

Oct 2019

Rik van Erp

In pigs, starch is digested into glucose in the small intestine. Undigested starch, i.e. resistant starch (RS), serves as substrate for microbial fermentation. The aim of this thesis was to improve understanding of underlying processes affecting the utilization of digested and fermented starch to ultimately predict the effect of starch digestion kinetics on pig performance more accurately. Despite the assumption that fermented starch yields less energy than digested starch, growth rates of pigs fed low RS and high RS diets are often the same when feed is available ad libitum. In Chapter 2, we hypothesized that RS affects nutrient digestion and digesta passage rate, and consequently feeding behavior, which ultimately affects growth performance of pigs under ad libitum conditions. In this study, pigs were fed either a high RS (HRS) or low RS (LRS) diet. Despite a substantial reduction in enzymatic digestible starch (LRS: 98% vs. HRS: 74%), carcass gain, slaughter quality parameters, and feed efficiency used for carcass gain were not affected by diet. Because dietary RS concentration did not affect digesta passage rate nor feeding behavior, we suggested that the difference in energy intake between fermentable and digestible starch was compensated for post-absorptively. The aim of Chapter 3 was to investigate maintenance energy requirements and the efficiency in which energy is used for growth (incremental energy efficiency) in slow- (SG) and fast growing (FG) pigs, which were fed either a slowly (SDS) or a rapidly digestible starch (RDS) diet. A slower rate of starch digestion was hypothesized to reduce fat depositing in pigs and be beneficial for slow growing pigs that are associated with a reduced insulin sensitivity. Gross energy intake was 6% greater in FG-pigs than in SG-pigs, whereas incremental energy efficiencies and fasting heat production were unaffected. We concluded that a lower energy intake rather than greater maintenance requirements or a lower energy efficiency explains slow growth of SG-pigs. No beneficial effects of SDS on energy utilization of SG-pigs were observed. RDS increased incremental use of energy for fat retention (2 %-units), which was most likely explained by greater levels of postprandial fat deposition. Microbial activity in the small intestine has shown to exist, which may result in an overestimation of starch digestion when not accounted for. In Chapter 4, we aimed to quantify both ileal and total tract starch fermentation and investigated the effect of RS on bacterial biomass formation and microbiota composition. A method based on the contrast in natural 13C-enrichment between starch and non-starch dietary components was used to quantify total tract fermentation of starch. Pigs were fed either a high RS (HRS) or low RS (LRS) diet. Microbiota composition in rectal digesta, but not in ileal digesta, slightly differed between diets. Total tract starch fermentation was 18 %-units greater in HRS-fed pigs than LRS-fed pigs (P<0.001). Large intestinal starch disappearance was 24 %-units greater in LRS-fed than HRS-fed pigs (P<0.001), implying that ileal starch fermentation was 6 %-units greater in HRS-fed pigs than LRS-fed pigs (P=0.046). The 13C-method used to estimate starch fermentation was reasonably close to colonic starch disappearance, but largely overestimated ileal starch fermentation. Our results suggested that ileal starch digestion in pigs can be overestimated with 1-7% when based on ileal starch disappearance. In Chapter 5, we hypothesized that alterations in feeding behavior to changes in RS intake may be dynamic, depending on the adaptation of processes involved when shifting from starch digestion to fermentation or vice versa. To test this hypothesis, we interchanged HRS and LRS in 5 steps, either in upwards (low to high; LH) or downwards (high to low; HL) direction. Complete substitution of LRS with HRS increased the proportion of starch fermented, which was greater in LH pigs (17.6%) than HL pigs (8.18%) and decreased feed intake (106 g/d) and meal size (12.6 g) of LH pigs, but not of HL pigs. We concluded that pigs adapt more slowly to increasing dietary supply of digestible starch than to RS, which resulted in fermentation of potentially enzymatically digestible starch. Furthermore, feed intake decreased only in pigs poorly adapting to RS; hence, the adequacy of adaptation, rather than RS itself reduced feed intake of pigs. Misalignment of the day/night rhythm with circadian feeding rhythms (circadian misalignment) has been shown to increase fat deposition and the risk for metabolic disorders in humans and rodents. In Chapter 6, we investigated the effects of circadian misalignment on energy expenditure in pigs. Pigs were fed either during the day (10.00h - 18.00h; diurnal feeding: DF) or night (22.00h - 06.00h; nocturnal feeding: NF), bihourly the same sequential meals, representing 15, 10, 25, 30 and 20 % of a similar daily allowance. Heat production was 3% lower for NF-pigs than DF-pigs increasing fat retention by 7% in NF-pigs. Methane production was 30% greater in NF-pigs than in DF-pig. We concluded that circadian misalignment has little effect on nutrient digestion, but alters nutrient partitioning, ultimately increasing fat deposition. The causality of the association between circadian misalignment and methane production rates remained to be investigated. In Chapter 7, I discussed the impact of starch digestion kinetics on growth performance, energy utilization, and meal patterns of pigs, by combining the results described in this thesis with existing literature. Rapidly digestible starch favors postprandial lipogenesis ultimately leading to an increase in fat deposition in pigs, whereas the extent of starch digestion, hence RS, did not affect growth performance of pigs. Consequently, net energy values of RS and digestible starch seem to be similar, particularly under ad libitum conditions. Finally, meal patterns may be determined by both dietary and animal-intrinsic effects. Substantial changes in RS intake (30% RS), however, did not affect meal patters of growing pigs.

Hydrogen and methane breath test results are negatively associated with IBS and may reflect transit time in post‐surgical patients

Article

Nov 2020

Background Contention surrounds hydrogen and methane breath tests as putative measures of small intestinal bacterial overgrowth. We aimed to explore the clinical characteristics associated with positive and negative results to help clarify their role. Methods 525 glucose hydrogen/methane breath tests completed over 3 years were analyzed to look for positively and negatively associated predictive factors. Characteristics such as height and weight and underlying medical conditions, medications, and surgical history were collated. Key results There were 85 and 42 positive hydrogen and methane tests, respectively. Patients with irritable bowel syndrome (IBS) (HR = 0.17, p = 0.004) and those with a higher body mass index (HR = 0.93, p = 0.004) were significantly less likely to have a positive test. Patients who underwent the test post‐surgically were significantly more likely to have a positive test (HR = 2.76, p = 0.001). A sub‐analysis of post‐surgical patients by type and region of surgical resection demonstrated that none were statistically more likely than the next to have a positive test. However, for the surgical group as a whole the number of motility‐depressing drugs taken (such as opioids) was associated with a significantly decreased likelihood of a positive test (HR = 0.752, p = 0.045). Conclusion Our data suggest that patients with a diagnosis of IBS are statistically less likely to have a positive test and it is of limited utility in this group. Post‐surgical patients are more likely to have a positive test, possibly secondary to fast transit rather than bacterial overgrowth, as suggested by a significantly negative association with motility‐suppressing drugs in this sub‐group.

Methane breath tests and blood sugar tests in children with suspected carbohydrate malabsorption

Article

Full-text available

Nov 2020

Carbohydrate malabsorption and subsequent gastrointestinal symptoms are a common clinical problem in pediatrics. Hydrogen (H2) and methane (CH4) breath tests are a cheap and non-invasive procedure for diagnosing fructose and lactose malabsorption (FM/LM) but test accuracy and reliability as well as the impact of non-hydrogen producers (NHP) is unclear. CH4 breath tests (MBT), blood sugar tests (BST) and clinical symptoms were compared with H2 breath tests (HBT) for FM/LM. 187/82 tests were performed in children (2 to 18 years) with unclear chronic/recurrent abdominal pain and suspected FM/LM. In FM and LM, we found a significant correlation between HBT and MBT/BST. In LM, MBT differentiated most of the patients correctly and BST might be used as an exclusion test. However, additional MBT and BST had no diagnostic advantage in FM. NHP still remain a group of patients, which cannot be identified using the recommended CH4 cut-off values in FM or LM. Reported symptoms during breath tests are not a reliable method to diagnose FM/LM. Overall a combined test approach might help in diagnosing children with suspected carbohydrate malabsorption.

Appendix. Gasotransmitters: Growing Pains and Joys

Chapter

Jun 2018

Rui Wang

Gasotransmitters are gas molecules produced endogenously in prokaryotic and eukaryotic cells for signalling purposes. This book provides, for the first time, a comprehensive description and systematic look at all gasotransmitters, established or proposed, since their detection in 2002. The content and scope covers the production, metabolism, and signalling roles of gasotransmitters. Conceptual advances, scientific discoveries and newly developed techniques described in this book influence our understanding of fundamental molecular and cellular events in biology and medicine. This book serves as the state-of-the-art book for undergraduate and graduate students as well as post-doctoral fellows in biomedical disciplines and toxicologists studying the toxic mechanisms of gasotransmitters in the environment. It will also be welcomed by researchers in university and research institutes, government agencies, pharmaceutical and medical instrument industry, and clinical practice.

Seasonal shifts in the gut microbiome indicate plastic responses to diet in wild geladas

Preprint

Full-text available

Jul 2020

Animals have evolved numerous strategies to cope with energetic challenges, with dynamic changes to the gut microbiome potentially constituting one such strategy. We tested how proxies of food availability (rainfall) and thermoregulatory stress (temperature) predicted gut microbiome composition of geladas (Theropithecus geladas), a grazing, high-altitude primate inhabiting a seasonal environment. The gelada gut microbiome varied across seasons, reflecting more efficient digestion of the primary foods eaten at certain times of year. In rainier periods, the gut was dominated by cellulolytic/fermentative bacteria that specialized in digesting grass, while during dry periods the gut was dominated by bacteria that break down starches found in underground plant parts. Temperature had a smaller, but detectable, effect on the gut microbiome. We found an increase in microbes involved in metabolism and energy production during cold and dry periods, suggesting buffering when thermoregulatory and nutritional stress co-occurred. Our results suggest that the gelada gut microbiome may shift to compensate for host diet and energetic demands.

Obesity, diabetes, and the gut microbiome: an updated review

Article

Oct 2018

Introduction: Obesity and diabetes are two of the most prevalent health problems and leading causes of death globally. As research on the intestinal microbiome increases, so does our understanding of its intricate relationship to these diseases, although this has yet to be fully elucidated. Areas covered: This review evaluates the role of the gut microbiome in obesity and diabetes, including the influences of internal and environmental factors. Literature searches were performed using the keywords ‘diabetes’; ‘insulin resistance’; ‘gut microbiome’; ‘gut microbes’; ‘obesity’; and ‘weight gain’. Expert commentary: Highlights of recent research include new findings regarding the effects of caloric restriction, which expound the importance of diet in shaping the gut microbiome; and studies reinforcing the lasting implications of antibiotic use for diabetes and obesity, particularly repeated doses in early childhood. Mechanistically, interactions between the microbiome and the host innate immune system, mediated by TLR4-LPS signaling, have been shown to meditate the metabolic benefits of caloric restriction. Further, gut microbes haven now been shown to regulate oxygen availability via butyrate production, thus protecting against the proliferation of pathogens such as E. coli and Salmonella. However, many microbial metabolites remain unidentified and their roles in obesity and diabetes remain to be determined

Chapter 8: Production and Signaling of Methane

Chapter

Jun 2018

Increase in breath hydrogen concentration was correlated with the main pancreatic duct stenosis

Article

Feb 2018

Background: Hydrogen is produced from unabsorbed carbohydrates in the intestine through degradation and metabolism by hydrogenase of intestinal bacteria. The hydrogen is then partially diffused into blood flow and released and detected in exhaled breath. Pancreatic juice production is decreased in patients with reduced pancreatic exocrine function, including those with pancreatic cancer, thus decreasing digestion and absorption of nutrients including carbohydrates, which may increase undigested carbohydrates in the intestine and increase breath hydrogen concentration (BHC). The aim of this study was to investigate the association between BHC and pancreatic diseases. Methods: A retrospective study was designed and 68 patients underwent morning fasting breath hydrogen test. Since there is no clear standard, normal breath hydrogen concentration, the median of the measured values from the subjects(9ppm) was adopted as the standard. The subjects were classified into those with a value exceeding the median (BHC high group:32 patients) and a value equal to or below the median (BHC low group:36 patients). Patients characteristics, blood test results and imaging findings characteristic of pancreatic diseases were compared between the groups. Results: The age was significantly higher (P=0.010) and the incidences of pancreatic ductal adenocarcinoma and autoimmune pancreatitis were significantly higher (P=0.018 and P=0.004, respectively) in the BHC high group. With respect to the blood test items, the Alb level was significantly lower in the BHC high group (P=0.005). With respect to the characteristic imaging findings of pancreatic diseases, the proportions of patients with pancreatic enlargement, the main pancreatic duct(MPD) stenosis, and the MPD dilatation were significantly higher in the BHC high group (P=0.022, P<0.001, and P=0.002, respectively). On univariate analysis, only the MPD stenosis was extracted as an independent factor (P=0.014). Conclusion: It was suggested that the fasting breath hydrogen concentration is associated with pancreatic diseases causing stenosis of the main pancreatic duct, including pancreatic cancer.&#13.

Methanobrevibacter smithii Is the Predominant Methanogen in Patients with Constipation-Predominant IBS and Methane on Breath

Article

Full-text available

May 2012
DIGEST DIS SCI

Purpose: Among irritable bowel syndrome (IBS) patients, breath methane producers overwhelmingly have constipation predominance (C-IBS). Although the most common methanogen in humans is Methanobrevibacter smithii, incidence and type of methanogenic bacteria in C-IBS patients are unknown. Methods: By use of a questionnaire and lactulose breath testing, subjects with Rome II C-IBS and methane (>3 ppm) were selected (n = 9). The control group included subjects with IBS who had no breath methane (n = 10). Presence of bacterial DNA was assessed in a stool sample of each subject by quantitative-PCR using universal 16S rDNA primer. M. smithii was quantified by use of a specific rpoB gene primer. Results: M. smithii was detected in both methane and non-methane subjects. However, counts and relative proportion of M. smithii were significantly higher for methane-positive than for methane-negative subjects (1.8 × 10(7) ± 3.0 × 10(7) vs 3.2 × 10(5) ± 7.6 × 10(5) copies/g wet stool, P < 0.001; and 7.1 ± 6.3 % vs 0.24 ± 0.47 %, P = 0.02 respectively). The minimum threshold of M. smithii resulting in positive lactulose breath testing for methane was 4.2 × 10(5) copies/g wet stool or 1.2 % of total stool bacteria. Finally, area-under-curve for breath methane correlated significantly with both absolute quantity and percentage of M. smithii in stool (R = 0.76; P < 0.001 and R = 0.77; P < 0.001 respectively). Conclusions: M. smithii is the predominant methanogen in C-IBS patients with methane on breath testing. The number and proportion of M. smithii in stool correlate well with amount of breath methane.

Intestinal Methane Production in Obese Individuals Is Associated with a Higher Body Mass Index

Article

Full-text available

Jan 2012

Obesity is an epidemic that affects 1 in 3 individuals in the United States, and recent evidence suggests that enteric microbiota may play a significant role in the development of obesity. This study evaluated the association between methanogenic archaea and obesity in human subjects. Subjects with a body mass index (BMI) of 30 kg/m² or higher were prospectively recruited from the weight loss program of a tertiary care medical center. Subjects who met the study's inclusion criteria were asked to complete a questionnaire that included a series of visual analogue scores for bowel symptom severities. Subjects then provided a single end-expiratory breath sample to quantitate methane levels. Bivariate and multivariate analyses were used to determine associations with BMI. A total of 58 patients qualified for enrollment. Twenty percent of patients (n = 12) had breath test results that were positive for methane (>3 parts per million [ppm]), with a mean breath methane concentration of 12.2±3.1 ppm. BMI was significantly higher in methane-positive subjects (45.2±2.3 kg/m²) than in methane-negative subjects (38.5±0.8 kg/m²; P=.001). Methane-positive subjects also had a greater severity of constipation than methane-negative subjects (21.3±6.4 vs 9.5±2.4; P=.043). Multiple regression analysis illustrated a significant association between BMI and methane, constipation, and antidepressant use. However, methane remained an independent predictor of elevated BMI when controlling for antidepressant use (P<.001) and when controlling for both constipation and antidepressant use (6.55 kg/m² greater BMI; P=.003). This is the first human study to demonstrate that a higher concentration of methane detected by breath testing is a predictor of significantly greater obesity in overweight subjects.

Gut Microbiota Fermentation of Prebiotics Increases Satietogenic and Incretin Gut Peptide Production With Consequences for Appetite Sensation and Glucose Response After a Meal

Article

Full-text available

Sep 2009
AM J CLIN NUTR

We have previously shown that gut microbial fermentation of prebiotics promotes satiety and lowers hunger and energy intake in humans. In rodents, these effects are associated with an increase in plasma gut peptide concentrations, which are involved in appetite regulation and glucose homeostasis. Our aim was to examine the effects of prebiotic supplementation on satiety and related hormones during a test meal for human volunteers by using a noninvasive micromethod for blood sampling to measure plasma gut peptide concentrations. This study was a randomized, double-blind, parallel, placebo-controlled trial. A total of 10 healthy adults (5 men and 5 women) were randomly assigned to groups that received either 16 g prebiotics/d or 16 g dextrin maltose/d for 2 wk. Meal tolerance tests were performed in the morning to measure the following: hydrogen breath test, satiety, glucose homeostasis, and related hormone response. We show that the prebiotic treatment increased breath-hydrogen excretion (a marker of gut microbiota fermentation) by approximately 3-fold and lowered hunger rates. Prebiotics increased plasma glucagon-like peptide 1 and peptide YY concentrations, whereas postprandial plasma glucose responses decreased after the standardized meal. The areas under the curve for plasma glucagon-like peptide 1 and breath-hydrogen excretion measured after the meal (0-60 min) were significantly correlated (r = 0.85, P = 0.007). The glucose response was inversely correlated with the breath-hydrogen excretion areas under the curve (0-180 min; r = -0.73, P = 0.02). Prebiotic supplementation was associated with an increase in plasma gut peptide concentrations (glucagon-like peptide 1 and peptide YY), which may contribute in part to changes in appetite sensation and glucose excursion responses after a meal in healthy subjects.

Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41

Article

Full-text available

Nov 2008
P NATL ACAD SCI USA

The distal human intestine harbors trillions of microbes that allow us to extract calories from otherwise indigestible dietary polysaccharides. The products of polysaccharide fermentation include short-chain fatty acids that are ligands for Gpr41, a G protein-coupled receptor expressed by a subset of enteroendocrine cells in the gut epithelium. To examine the contribution of Gpr41 to energy balance, we compared Gpr41−/− and Gpr41+/+ mice that were either conventionally-raised with a complete gut microbiota or were reared germ-free and then cocolonized as young adults with two prominent members of the human distal gut microbial community: the saccharolytic bacterium, Bacteroides thetaiotaomicron and the methanogenic archaeon, Methanobrevibacter smithii. Both conventionally-raised and gnotobiotic Gpr41−/− mice colonized with the model fermentative community are significantly leaner and weigh less than their WT (+/+) littermates, despite similar levels of chow consumption. These differences are not evident when germ-free WT and germ-free Gpr41 knockout animals are compared. Functional genomic, biochemical, and physiologic studies of germ-free and cocolonized Gpr41−/− and +/+ littermates disclosed that Gpr41-deficiency is associated with reduced expression of PYY, an enteroendocrine cell-derived hormone that normally inhibits gut motility, increased intestinal transit rate, and reduced harvest of energy (short-chain fatty acids) from the diet. These results reveal that Gpr41 is a regulator of host energy balance through effects that are dependent upon the gut microbiota. • host-microbial interactions • energy balance • enteroendocrine cells • nutrient sensing • polysaccharide fermentation

The gut microbiota as an environmental factor that regulates fat storage

Article

Full-text available

Dec 2004

New therapeutic targets for noncognitive reductions in energy intake, absorption, or storage are crucial given the worldwide epidemic of obesity. The gut microbial community (microbiota) is essential for processing dietary polysaccharides. We found that conventionalization of adult germ-free (GF) C57BL/6 mice with a normal microbiota harvested from the distal intestine (cecum) of conventionally raised animals produces a 60% increase in body fat content and insulin resistance within 14 days despite reduced food intake. Studies of GF and conventionalized mice revealed that the microbiota promotes absorption of monosaccharides from the gut lumen, with resulting induction of de novo hepatic lipogenesis. Fasting-induced adipocyte factor (Fiaf), a member of the angiopoietin-like family of proteins, is selectively suppressed in the intestinal epithelium of normal mice by conventionalization. Analysis of GF and conventionalized, normal and Fiaf knockout mice established that Fiaf is a circulating lipoprotein lipase inhibitor and that its suppression is essential for the microbiota-induced deposition of triglycerides in adipocytes. Studies of Rag1-/- animals indicate that these host responses do not require mature lymphocytes. Our findings suggest that the gut microbiota is an important environmental factor that affects energy harvest from the diet and energy storage in the host. • symbiosis • nutrient processing • energy storage • adiposity • fasting-induced adipose factor

Obesity alters gut microbial ecology

Article

Full-text available

Sep 2005

We have analyzed 5,088 bacterial 16S rRNA gene sequences from the distal intestinal (cecal) microbiota of genetically obese ob/ob mice, lean ob/+ and wild-type siblings, and their ob/+ mothers, all fed the same polysaccharide-rich diet. Although the majority of mouse gut species are unique, the mouse and human microbiota(s) are similar at the division (superkingdom) level, with Firmicutes and Bacteroidetes dominating. Microbial-community composition is inherited from mothers. However, compared with lean mice and regardless of kinship, ob/ob animals have a 50% reduction in the abundance of Bacteroidetes and a proportional increase in Firmicutes. These changes, which are division-wide, indicate that, in this model, obesity affects the diversity of the gut microbiota and suggest that intentional manipulation of community structure may be useful for regulating energy balance in obese individuals. • energy balance/obesity • host-microbial interactions • intestinal bacterial diversity • ob/ob mice • phylogenetics

Samuel BS, Gordon JI.. A humanized gnotobiotic mouse model of host-archaeal-bacterial mutualism. Proc Natl Acad Sci USA 103: 10011-10016

Article

Full-text available

Jul 2006

Our colons harbor trillions of microbes including a prominent archaeon, Methanobrevibacter smithii. To examine the contributions of Archaea to digestive health, we colonized germ-free mice with Bacteroides thetaiotaomicron, an adaptive bacterial forager of the polysaccharides that we consume, with or without M. smithii or the sulfate-reducing bacterium Desulfovibrio piger. Whole-genome transcriptional profiling of B. thetaiotaomicron, combined with mass spectrometry, revealed that, unlike D. piger, M. smithii directs B. thetaiotaomicron to focus on fermentation of dietary fructans to acetate, whereas B. thetaiotaomicron-derived formate is used by M. smithii for methanogenesis. B. thetaiotaomicron–M. smithii cocolonization produces a significant increase in host adiposity compared with monoassociated, or B. thetaiotaomicron–D. piger biassociated, animals. These findings demonstrate a link between this archaeon, prioritized bacterial utilization of polysaccharides commonly encountered in our modern diets, and host energy balance. • adiposity • energy homeostasis • gut microbial ecology • polysaccharide metabolism • Methanobrevibacter smithii

Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027-1031

Article

Full-text available

Jan 2007
NATURE

The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.

Microbial Ecology: Human gut microbes associated with obesity

Article

Full-text available

Jan 2007
NATURE

Two groups of beneficial bacteria are dominant in the human gut, the Bacteroidetes and the Firmicutes. Here we show that the relative proportion of Bacteroidetes is decreased in obese people by comparison with lean people, and that this proportion increases with weight loss on two types of low-calorie diet. Our findings indicate that obesity has a microbial component, which might have potential therapeutic implications.

Cause-Specific Excess Deaths Associated With Underweight, Overweight, and Obesity

Article

Full-text available

Nov 2007
J Am Med Assoc

Context: The association of body mass index (BMI) with cause-specific mortality has not been reported for the US population. Objective: To estimate cause-specific excess deaths associated with underweight (BMI <18.5), overweight (BMI 25-<30), and obesity (BMI > or =30). Design, setting, and participants: Cause-specific relative risks of mortality from the National Health and Nutrition Examination Survey (NHANES) I, 1971-1975; II, 1976-1980; and III, 1988-1994, with mortality follow-up through 2000 (571,042 person-years of follow-up) were combined with data on BMI and other covariates from NHANES 1999-2002 with underlying cause of death information for 2.3 million adults 25 years and older from 2004 vital statistics data for the United States. Main outcome measures: Cause-specific excess deaths in 2004 by BMI levels for categories of cardiovascular disease (CVD), cancer, and all other causes (noncancer, non-CVD causes). Results: Based on total follow-up, underweight was associated with significantly increased mortality from noncancer, non-CVD causes (23,455 excess deaths; 95% confidence interval [CI], 11,848 to 35,061) but not associated with cancer or CVD mortality. Overweight was associated with significantly decreased mortality from noncancer, non-CVD causes (-69 299 excess deaths; 95% CI, -100 702 to -37 897) but not associated with cancer or CVD mortality. Obesity was associated with significantly increased CVD mortality (112,159 excess deaths; 95% CI, 87,842 to 136,476) but not associated with cancer mortality or with noncancer, non-CVD mortality. In further analyses, overweight and obesity combined were associated with increased mortality from diabetes and kidney disease (61 248 excess deaths; 95% CI, 49 685 to 72,811) and decreased mortality from other noncancer, non-CVD causes (-105,572 excess deaths; 95% CI, -161 816 to -49,328). Obesity was associated with increased mortality from cancers considered obesity-related (13,839 excess deaths; 95% CI, 1920 to 25,758) but not associated with mortality from other cancers. Comparisons across surveys suggested a decrease in the association of obesity with CVD mortality over time. Conclusions: The BMI-mortality association varies by cause of death. These results help to clarify the associations of BMI with all-cause mortality.

Ability of new octapolar bioimpedance spectroscopy analyzers to predict 4-component–model percentage body fat in Hispanic, black, and white adults

Article

Full-text available

Feb 2008

New, vertical, 8-electrode bioimpedance spectroscopy (BIS) analyzers provide detailed body-composition and nutritional information within 2 min. This is the first report on BIS's accuracy in predicting relative fatness [percentage body fat (%BF)] in a heterogeneous sample according to a multicomponent model criterion. We compared %BF measurements from 2 BIS devices with those from a multicomponent model in a sample of Hispanic, black, and white adults. Equal numbers of apparently healthy men and women (n = 75 of each) from each racial-ethnic group, diverse in body mass index and age, volunteered. Reference %BF (%BF(4C)) was computed by using a 4-component (4C) model with total bone mineral content obtained from dual-energy X-ray absorptiometry, body density from underwater weighing with measured residual lung volume, and total body water from traditional BIS. Estimations from InBody 720 (%BF(720)) and InBody 320 (%BF(320)) BIS analyzers were validated against %BF(4C). The %BF(720) (r = 0.85, SEE = 5.19%BF) and %BF(320) (r = 0.84, SEE = 5.17%BF) correlations were significant (P < 0.05) in the men; main effects were nonsignificant. Correlations for %BF(720) (r = 0.88, SEE = 4.85%BF) and %BF(320) (r = 0.89, SEE = 4.82%BF) also were significant in the women (P < 0.05); there was a main effect for method but not race-ethnicity. There were no sex-specific overestimations or underestimations at the extremes of the distributions. BIS estimates of %BF(4C) were well correlated in men and women. There were no significant methodologic differences in the men. The %BF(4C) was significantly underestimated by %BF(720) and %BF(320) in the women.

Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet-Induced Obesity and Diabetes in Mice

Article

Full-text available

Jul 2008

Diabetes and obesity are characterized by a low-grade inflammation whose molecular origin is unknown. We previously determined, first, that metabolic endotoxemia controls the inflammatory tone, body weight gain, and diabetes, and second, that high-fat feeding modulates gut microbiota and the plasma concentration of lipopolysaccharide (LPS), i.e., metabolic endotoxemia. Therefore, it remained to demonstrate whether changes in gut microbiota control the occurrence of metabolic diseases. We changed gut microbiota by means of antibiotic treatment to demonstrate, first, that changes in gut microbiota could be responsible for the control of metabolic endotoxemia, the low-grade inflammation, obesity, and type 2 diabetes and, second, to provide some mechanisms responsible for such effect. We found that changes of gut microbiota induced by an antibiotic treatment reduced metabolic endotoxemia and the cecal content of LPS in both high-fat-fed and ob/ob mice. This effect was correlated with reduced glucose intolerance, body weight gain, fat mass development, lower inflammation, oxidative stress, and macrophage infiltration marker mRNA expression in visceral adipose tissue. Importantly, high-fat feeding strongly increased intestinal permeability and reduced the expression of genes coding for proteins of the tight junctions. Furthermore, the absence of CD14 in ob/ob CD14(-)(/)(-) mutant mice mimicked the metabolic and inflammatory effects of antibiotics. This new finding demonstrates that changes in gut microbiota controls metabolic endotoxemia, inflammation, and associated disorders by a mechanism that could increase intestinal permeability. It would thus be useful to develop strategies for changing gut microbiota to control, intestinal permeability, metabolic endotoxemia, and associated disorders.

Mechanism underlying the resistance to diet-included in germ-free mice

Article

Jan 2007

Energetics of syntrophic cooperation in methanogenic degradation

Article

Jun 1997

Bernhard Schink

Dental Prophylaxis and Periodontal Treatment are Protective Factors to Ischemic Stroke

Article

Jul 2013
J EMERG MED

Elaine Reno

Intestinal Methanobrevibacter smithii but Not Total Bacteria Is Related to Diet-Induced Weight Gain in Rats

Article

Apr 2013
OBESITY

It is increasingly understood that gastrointestinal (GI) methanogens, including Methanobrevibacter smithii, influence host metabolism. Therefore, we compared M. smithii colonization and weight gain in a rat model under different dietary conditions. Sprague-Dawley rats were inoculated with M. smithii or vehicle (N = 10/group), fed normal chow until day 112 postinoculation, high-fat chow until day 182, then normal chow until day 253. Thereafter, five rats from each group were fed high-fat and normal chow until euthanasia. Both groups exhibited M. smithii colonization, which increased following inoculation only for the first 9 days. Change to high-fat chow correlated with significant increases in weight (P < 0.00001) and stool M. smithii (P < 0.01) in all rats, with stool M. smithi decreasing on return to normal chow. Rats switched back to high-fat on day 253 further increased weight (P < 0.001) and stool M. smithii (P = 0.039). Euthanasia revealed all animals had higher M. smithii, but not total bacteria, in the small intestine than in the colon. Rats switched back to high-fat chow had higher M. smithii levels in the duodenum, ileum, and cecum than those fed normal chow; total bacteria did not differ in any bowel segment. Rats which gained more weight had more bowel segments colonized, and the lowest weight recorded was in a rat on high-fat chow which had minimal M. smithii colonization. We conclude that M. smithii colonization occurs in the small bowel as well as in the colon, and that the level and extent of M. smithii colonization is predictive of degree of weight gain in this animal model.

Carbohydrates and dietary fibre

Article

Feb 2007
Nutr Bull

Summary The health benefits of including sufficient dietary fibre in the diet have been well described and have formed the basis of dietary recommendations around the world. However, dietary fibre is a complex dietary entity, consisting of many non-digestible components of food. Debate surrounding the definition and measurement of dietary fibre has resulted in inconsistencies in labelling, description and recommendations set across the world. In the UK, dietary recommendations are made using the fraction of non-digestible material described as non-starch polysaccharide that is measured by the Englyst method. However, the Association of Official Analytical Chemists (AOAC) methods, used widely by the food industry, capture a much greater range of non-digestible material, that some suggest should be included in any definition of dietary fibre. An attempt to resolve such discrepancies, possibly by taking an approach that considers the health effects of fractions not captured in the Englyst method, is probably overdue. Additionally, it is clear that the effects of these various non-digestible components of dietary fibre are not interchangeable, and it is important that fibre comes from a range of sources to ensure maximum health benefits from the fibre in the diet. Traditional ‘insoluble’ fibres are required to add bulk as well as rapidly fermentable, viscous fibres to bring about cholesterol lowering. There is also a convincing argument for including slowly fermented components, such as resistant starches, that are well tolerated in the digestive system and can bring about improvements in gut function. Currently there is insufficient data from well designed human intervention trials to make specific recommendations on the amounts of these fibre components in the diet, but it may be useful for health professionals to talk in terms of the different food sources of these types of fibre, as well as total fibre amounts.

Comparative study of hydrogen and methane production in the human colon using caecal and faecal homogenates

Article

Jul 1990

Rates of hydrogen and methane production were compared in caecal and faecal homogenates in six methane producers. Faecal homogenates produced hydrogen and methane in the absence of and after the addition of lactulose, whereas caecal homogenates produced hydrogen but little methane.

The Development of Methane Production in Childhood and Adolescence

Article

Sep 1985
J PEDIATR GASTR NUTR

Methane concentration in the expired air was analyzed in 393 infants, children, and adolescents. There was no methane production below the age of 3 years. In the age group 3-4 years, 6.4% of the children produced methane. The percentages were 14.3-18.2% in children aged 7-14. A rise in methane production to 39.4-45.9% was recorded from age 14 to 18, as compared with 49.4% in adults in Israel. The reasons for these changes in methane production with age are not known. Alterations in the colonic flora or the production of a specific substrate(s) are the main possibilities. In our opinion, the latter possibility deserves further investigation.

Schink B.. Energetics of syntrophic cooperation in methanogenic degradation. Microbiol Mol Biol Rev 61: 262-280

Article

Jul 1997

B Schink

Fatty acids and alcohols are key intermediates in the methanogenic degradation of organic matter, e.g., in anaerobic sewage sludge digestors or freshwater lake sediments. They are produced by classical fermenting bacteria for disposal of electrons derived in simultaneous substrate oxidations. Methanogenic bacteria can degrade primarily only one-carbon compounds. Therefore, acetate, propionate, ethanol, and their higher homologs have to be fermented further to one-carbon compounds. These fermentations are called secondary or syntrophic fermentations. They are endergonic processes under standard conditions and depend on intimate coupling with methanogenesis. The energetic situation of the prokaryotes cooperating in these processes is problematic: the free energy available in the reactions for total conversion of substrate to methane attributes to each partner amounts of energy in the range of the minimum biochemically convertible energy, i.e., 20 to 25 kJ per mol per reaction. This amount corresponds to one-third of an ATP unit and is equivalent to the energy required for a monovalent ion to cross the charged cytoplasmic membrane. Recent studies have revealed that syntrophically fermenting bacteria synthesize ATP by substrate-level phosphorylation and reinvest part of the ATP-bound energy into reversed electron transport processes, to release the electrons at a redox level accessible by the partner bacteria and to balance their energy budget. These findings allow us to understand the energy economy of these bacteria on the basis of concepts derived from the bioenergetics of other microorganisms.

Methane Production During Lactulose Breath Test Is Associated with Gastrointestinal Disease Presentation

Article

Jan 2003

It has recently been determined that there is an increased prevalence of bacterial overgrowth in IBS. Since there are two gases (hydrogen and methane) measured on lactulose breath testing, we evaluated whether the different gas patterns on lactulose breath testing coincide with diarrhea and constipation symptoms in IBS and IBD. Consecutive patients referred to the gastrointestinal motility program at Cedars-Sinai Medical Center for lactulose breath testing were given a questionnaire to evaluate their gastrointestinal symptoms. Symptoms were graded on a scale of 0-5. Upon completion of the breath test, the results were divided into normal, hydrogen only, hydrogen and methane, and methane only positive breath tests. A comparison of all subjects and IBS subjects was undertaken to evaluate diarrhea and constipation with regards to the presence or absence of methane. This was further contrasted to Crohn's and ulcerative colitis (UC) patients in the database. After exclusion criteria, 551 subjects from the database were available for comparison. Of the 551 subjects (P < 0.05, one-way ANOVA) and in a subgroup of 296 IBS subjects (P < 0.05, one-way ANOVA), there was a significant association between the severity of reported constipation and the presence of methane. The opposite was true for diarrhea (P < 0.001). If a breath test was methane positive, this was 100% associated with constipation predominant IBS. Furthermore, IBS had a greater prevalence of methane production than Crohn's or UC. In fact, methane was almost nonexistent in the predominantly diarrheal conditions of Crohn's and UC. In conclusion, a methane positive breath test is associated with constipation as a symptom.

Methane, a gas produced by enteric bacteria, slows intestinal transit and augments small intestinal contractile activity

Article

Jun 2006

The presence of methane on lactulose breath test among irritable bowel syndrome (IBS) subjects is highly associated with the constipation-predominant form. Therefore, we set out to determine whether methane gas can alter small intestinal motor function. In dogs, small intestinal fistulae were created to permit measurement of intestinal transit. Using a radiolabel, we evaluated transit during infusion of room air and subsequently methane. In this model, small intestinal infusion of methane produced a slowing of transit in all dogs by an average of 59%. In a second experiment, guinea pig ileum was pinned into an organ bath for the study of contractile activity in response to brush strokes applied to the mucosa. The force of contraction was measured both orad and aborad to the stimulus. The experiment was repeated while the bath was gassed with methane. Contractile activities orad and aborad to the stimulus were significantly augmented by methane compared with room air (P < 0.05). In a third experiment, humans with IBS who had undergone a small bowel motility study were compared such that subjects who produced methane on lactulose breath test were compared with those producing hydrogen. The motility index was significantly higher in methane-producing IBS patients (1,851 +/- 861) compared with hydrogen producers (1,199 +/- 301) (P < 0.05). Therefore, methane, a gaseous by-product of intestinal bacteria, slows small intestinal transit and appears to do so by augmenting small bowel contractile activity.

The medical complications of Obesity

Article

Oct 2006

The prevalence of overweight and obesity is increasing worldwide.1 A comparison of data from 1976–802 with that from 1999–2000 shows that the prevalence of overweight (defined as body mass index, BMI, of 25–29.9 kg/m2) increased from 46% to 64.5%, and the prevalence of obesity (BMI ⩾ 30 kg/m2) doubled to 30.5%. The epidemic of obesity is not just isolated to the US, but is worldwide,3,,4 including less affluent countries.4 Obesity and overweight have many causes, including genetic, metabolic, behavioural and environmental. The rapid increase in prevalence suggests that behavioural and environmental influences predominate, rather than biological changes. We summarize data from many studies evaluating the impact of obesity on mortality and morbidity, discuss some controversies and provide practical guidelines for managing obese patients. Direct associations between obesity and several diseases, including diabetes mellitus, hypertension, dyslipidaemia and ischaemic heart disease, are well recognized. Despite this, the relationship between body weight and all-cause mortality is more controversial. A very high degree of obesity (BMI ⩾35 kg/m2) seems to be linked to higher mortality rates,5 but the relationship between more modest degrees of overweight and mortality is unclear. Initial data from actuarial studies of more than 4 million men and women showed a direct positive association between body weight and overall mortality rates.6 Subsequent studies confirmed increased mortality risk above a certain threshold, but found a U-shaped association between weight and mortality.7,,8 In the Build study,9 there was a higher mortality in lean subjects, but there was no adjustment for smoking. The American Cancer Society found a much stronger association between leanness and mortality, specifically cancer mortality, in the group of smokers compared to non-smokers.10 The Harvard Alumni Study11 was a prospective cohort study of more than 19 000 middle-aged … Address correspondence to Dr S.D.H. Malnick, Department of Internal Medicine C, Kaplan Medical Centre, Rehovot 76100, Israel. email: stevash{at}trendline.co.il

Backhed F, Manchester JK, Semenkovich CF, Gordon JI.. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci USA 104: 979-984

Article

Feb 2007

The trillions of microbes that colonize our adult intestines function collectively as a metabolic organ that communicates with, and complements, our own human metabolic apparatus. Given the worldwide epidemic in obesity, there is interest in how interactions between human and microbial metabolomes may affect our energy balance. Here we report that, in contrast to mice with a gut microbiota, germ-free (GF) animals are protected against the obesity that develops after consuming a Western-style, high-fat, sugar-rich diet. Their persistently lean phenotype is associated with increased skeletal muscle and liver levels of phosphorylated AMP-activated protein kinase (AMPK) and its downstream targets involved in fatty acid oxidation (acetylCoA carboxylase; carnitine-palmitoyltransferase). Moreover, GF knockout mice lacking fasting-induced adipose factor (Fiaf), a circulating lipoprotein lipase inhibitor whose expression is normally selectively suppressed in the gut epithelium by the microbiota, are not protected from diet-induced obesity. Although GF Fiaf-/- animals exhibit similar levels of phosphorylated AMPK as their wild-type littermates in liver and gastrocnemius muscle, they have reduced expression of genes encoding the peroxisomal proliferator-activated receptor coactivator (Pgc-1alpha) and enzymes involved in fatty acid oxidation. Thus, GF animals are protected from diet-induced obesity by two complementary but independent mechanisms that result in increased fatty acid metabolism: (i) elevated levels of Fiaf, which induces Pgc-1alpha; and (ii) increased AMPK activity. Together, these findings support the notion that the gut microbiota can influence both sides of the energy balance equation, and underscore the importance of considering our metabolome in a supraorganismal context.

A humanized gnotobiotic mouse model of host-archaeal-bacterial mutualism

Jan 2006
10011

Samuel

An obesity-associated gut microbiome with increased capacity for energy harvest

Jan 2006
1027

Turnbaugh

Methane and Hydrogen Positivity on Breath Test Is Associated With Greater Body Mass Index and Body Fat

Abstract

No full-text available

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